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PLoS Pathog. 2014 Mar 20;10(3):e1004026. doi: 10.1371/journal.ppat.1004026. eCollection 2014 Mar.

The role of host and microbial factors in the pathogenesis of pneumococcal bacteraemia arising from a single bacterial cell bottleneck.

Author information

1
LAMMB, Department of Biotechnology, University of Siena, Siena, Italy.
2
Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy.
3
Department of Mathematics, University of Leicester, Leicester, United Kingdom.
4
Centro NMR, University of Siena, Siena, Italy.
5
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
6
LAMMB, Department of Biotechnology, University of Siena, Siena, Italy; UOC Batteriologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
7
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
8
Department of Neurology, Ludwig-Maximilians University of Munich, München, Germany.
9
Division of Medical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
10
LAMMB, Department of Biotechnology, University of Siena, Siena, Italy; UOC Batteriologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Department of Genetics, University of Leicester, Leicester, United Kingdom.

Abstract

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease.

PMID:
24651834
PMCID:
PMC3961388
DOI:
10.1371/journal.ppat.1004026
[Indexed for MEDLINE]
Free PMC Article

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